Complementary Therapies in Clinical Practice 39 (2020) 101166

Contents lists available at ScienceDirect

Complementary Therapies in Clinical Practice

journal homepage: http://www.elsevier.com/locate/ctcp

Respiratory rehabilitation in elderly patients with COVID-19: A randomized

controlled study
Kai Liu a, 1, Weitong Zhang b, 1, Yadong Yang c, 1, Jinpeng Zhang c, 1, Yunqian Li a, Ying Chen d, *
a
Department of Geriatric Center, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, 570311, PR China
b
Department of General Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, 570311, PR China
c
Department of Critical Care Medcine, Huanggang Central Hospital, Hubei Province. Huanggang, 438000, PR China
d
Department of Medical Laboratory, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, 570311, China

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Different degrees of disorders are reported in respiratory function, physical function and psycho­
Elderly logical function in patients with corona virus disease 2019 (COVID-19), especially in elderly patients. With the
Covid-19 experience of improved and discharged COVID-19 patients, timely respiratory rehabilitation intervention may
Respiratory rehabilitation
improve prognosis, maximize functional preservation and improve quality of life (QoL), but there lacks of studies
Pulmonary function
Quality of life
worldwide exploring the outcome of this intervention.
Psychological state Objective: To investigate the effects of 6-week respiratory rehabilitation training on respiratory function, QoL,
mobility and psychological function in elderly patients with COVID-19.
Methods: This paper reported the findings of an observational, prospective, quasi-experimental study, which
totally recruited 72 participants, of which 36 patients underwent respiratory rehabilitation and the rest without
any rehabilitation intervention. The following outcomes were measured: pulmonary function tests including
plethysmography and diffusing lung capacity for carbon monoxide (DLCO), functional tests (6-min walk distance
test), Quality of life (QoL) assessments (SF-36 scores), activities of daily living (Functional Independence Mea­
sure, FIM scores), and mental status tests (SAS anxiety and SDS depression scores).
Results: After 6 weeks of respiratory rehabilitation in the intervention group, there disclosed significant differ­
ences in FEV1(L), FVC(L), FEV1/FVC%, DLCO% and 6-min walk test. The SF-36 scores, in 8 dimensions, were
statistically significant within the intervention group and between the two groups. SAS and SDS scores in the
intervention group decreased after the intervention, but only anxiety had significant statistical significance
within and between the two groups.
Conclusions: Six-week respiratory rehabilitation can improve respiratory function, QoL and anxiety of elderly
patients with COVID-19, but it has little significant improvement on depression in the elderly.

1. Introduction
2019-novel coronaviruses belong to the β species of coronaviruses,
which mainly transmitted through respiratory droplets and close con­
tact, and it can be found in human respiratory epithelial cells in about
96 h, which firstly attacks the lungs and induces serous fluid, fibrin
exudates, and hyaline membrane formation in the alveoli [1]. COVID-19
infection is furiously spreading at an alarming rate, with a cumulative
number of 116,736 confirmed cases and 5701 deaths outside China to
date. As the earliest epidemic area, China has achieved a major victory
in the cooperation of the people through the efforts of the government.
At present, a total of 70,547 cases have been cured and discharged in
China. In this outbreak, the elderly population is generally susceptible
with high incidence of severe disease and mortality [2].
Community-acquired pneumonia in the elderly population has been
found to result in decreased activities of daily living (ADL) and QoL,
accompanied by decreased physical and mental function [3]. Respira­
tory disorders and lack of exercise in the elderly can lead to diseases such
as apraxia syndrome and pulmonary infections [4]. Therefore, for
elderly patients who suffered from COVID-19 and discharged with
satisfying results, improved respiratory function is an important factor
in maintaining ADL and QoL of the elderly.

* Corresponding author.
E-mail address: hkchenying@126.com (Y. Chen).
1
Contributed equally.

https://doi.org/10.1016/j.ctcp.2020.101166
Received 30 March 2020; Accepted 30 March 2020
Available online 1 April 2020
1744-3881/Published by Elsevier Ltd.
K. Liu et al.
Respiratory rehabilitation can improve respiratory function and QoL
in patients with chronic obstructive pulmonary disease (COPD) [5].
However, the effect of respiratory rehabilitation on respiratory function
and QoL in older adults with COVID-19 is unknown. Studies have
evaluated respiratory function in elderly patients with COPD, including
those with suspected COPD, who have better respiratory rehabilitation
[6]. Thus, in this study, we conducted a randomized controlled trial to
investigate the effects of respiratory rehabilitation on respiratory func­
tion, ADL, QoL, and psychological status in elderly patients with
COVID-19 who were discharged from the hospital with satisfying
results.
2. Method
Participants: were recruited from Hainan General Hospital central
hospital and Huanggang Central hospital, which were designated by the
government to admit COVID-19 from January 1, 2020 to February 6,
2020. Inclusion Criteria: (1) with a definite diagnosis of COVID-19; (2)
aged 65 years or above; (3) � 6 months after the onset of other acute
diseases; (4) mini-mental state examination (MMSE) score > 21; (6) no
COPD or any other respiratory disease; and (7) forced expiratory volume
in 1 s (FEV1) � 70%. Exclusion criteria: (1) moderate or severe heart
disease (Grade III or IV, New York Heart Association); (2) with severe
ischemic or hemorrhagic stroke or neurodegenerative diseases.
Study Design: This study is an open randomized controlled trial.
Participants were aware of all rehabilitation procedures, including res­
piratory rehabilitation (2 sessions per week for 6 weeks), once a day for
10 min. The demographic characteristics of each subject were assessed
prior to randomizing the subject. Odd numbers of patients were in the
intervention group while even numbers of patients in the control group
using a computer-generated allocation order. Interventions included: (1)
respiratory muscle training; (2) cough exercise; (3) diaphragmatic
training; (4) stretching exercise; and (5) home exercise. For respiratory
muscle training, participants used a commercial hand-held resistance
device (Threshold PEP; Philips Co.) for three sets with 10 breaths in each
set; parameters were set at 60% of the individual’s maximal expiratory
mouth pressure, with a rest period of 1 min between the two sets. Three
sets of 10 active coughs were adopted for cough exercises. For dia­
phragmatic training, each participant performed 30 maximal voluntary
diaphragmatic contractions in the supine position, placing a medium
weight (1–3 kg) on the anterior abdominal wall to resist diaphragmatic
descent. In stretching exercises, the respiratory muscles are stretched
under the guidance of a rehabilitation therapist. The patient was placed
in the supine or lateral decubitus position with the knees bent to correct
the lumbar curve. Patients were ordered to move their arms in flexion,
horizontal extension, abduction, and external rotation. In terms of home
exercises, subjects were instructed in pursed-lip breathing and coughing
training, and asked to undergo 30 sets per day.
2.1. Assessment
Primary Outcome Measures: Respiratory function; Secondary
Outcome Measures: Exercise endurance (6-min walk distance), ADL and
QoL, psychological status assessment (anxiety, depression scores).
Respiratory function, by automated computerized spirometer
(Model ML3500S) of Micro Direct, for assessing respiratory function.
The following parameters related to respiratory function were
measured: (1) forced expiratory volume in 1 second (FEV1); (2) forced
vital capacity (FVC); (3) DLCO (%) refers to the amount of CO that
passes through the alveolar capillary membrane into the capillary blood
per unit time, per unit pressure difference with a percentage of the
measured value to the predicted value > 80% as normal.
Exercise endurance, which measured under the 6-min walk test
(6MWT), is the distance one walks within 6 min (also known as the
dynamic distance). Percutaneous oxygen saturation (SpO2), heart rate,
systolic blood pressure, diastolic blood pressure, respiratory rate and
2
Complementary Therapies in Clinical Practice 39 (2020) 101166
perceived exertion (Borg scale) were measured before and after a 6-min
walk using a saturated pulse oximeter.
Activities of daily living(ADL) The rehabilitation therapist assessed
ADL with the Functional Independence Measure (FIM) scale. The FIM
contains 18 items, each with a maximum score of 7 points, minimum
score of 1 point, and a maximum total score of 126 points. The 18 items
of the FIM can be divided into 13 items for assessing motor ADL
(including 6 self-care items, 2 sphincter control items, 3 transfer items,
and 2 motor items) and 5 items for assessing cognitive ADL (including 2
items) for communication and 3 items for social cognition).
QoL Assessment The QoL of patients in the two groups before and
after nursing intervention was assessed using the Short Form-36 (SF-36).
The SF-36 scale had 8 dimensions, and each dimension was converted
into a percentage score. The higher score, the better QoL.
Assessment of Anxiety, Depression Self-rating depression scale
(SDS) and self-rating anxiety scale (SAS) were exploited to assess
depression and anxiety in the two groups 2 days after the intervention.
Both SDS and SAS have 20 items, each of which was scored on a scale of
1–4, and the higher score, the more severe the degree of depression and
anxiety.
Study Termination The study was terminated when any of the
following was reached: worsening of subjective symptoms (dyspnea);
SpO2 decreased by 85% or less; the heart rate increased to 85% or more
of the predicted maximum heart rate.
2.2. Statistical analysis
SPSS 24.0 was used for all statistical analysis. The minimum sample
size of each group was 26, power was 80%, and an α error was 5%. The
magnitudes of the effects were calculated using the Mann Whitney U test
with Cohen’d coefficient set to 0.8. Therefore, the sample size of this
study (n ¼ 72) has sufficient detection ability. To ensure a balanced
random distribution, Fisher’s exact test was used for gender differences
between the intervention group and the control group at baseline, and
unpaired t-test was used for age and other variable evaluation. Wilcoxon
rank sum test was used to compare the results of each group with the
baseline indicators. Using Mann Whitney U test to compare the differ­
ence between the two groups, the statistical significance was set as P <
0.05.
Ethical considerations The survey was conducted with the approval
of the ethics committees of Hainan General Hospital and Huanggang
Central Hospital (approval numbers: 19758 and 20200125). All partic­
ipants provided written informed consent after receiving a complete
written description of the trial.
3. Results
A total of 92 patients were assessed for eligibility. Among them, 9
patients disagreed with this study, 3 patients with FEV1 � 70%, 4 pa­
tients severe heart disease, and the remaining 76 patients were ran­
domized. Of the 38 patients in the intervention group, 2 patients
abandoned before completing all 12 sessions and were unable to
continue rehabilitation. Of the 38 patients in the control group, 2 were
also unable to continue rehabilitation. Finally, a total of 72 patients
completed the study, of whom 36 completed the respiratory rehabili­
tation program.
Baseline Characteristics There were no statistically significant
differences between the two groups of patients in age, gender, BMI,
extent of lung CT lesions, past medical history (Table 1).
Pulmonary Function Test The intervention group and the control
group were compared after 6 weeks of respiratory rehabilitation, and
found that there was a statistically significant difference between FEV1
(L), FVC (L), FEV1/FVC% and DLCO% (Fig. 1, Fig. 2, Table 2).
Exercise Capacity Test The 6-min walk distance after 6 weeks of
respiratory rehabilitation within the intervention group was signifi­
cantly longer than that before the intervention, which was statistically
K. Liu et al. Complementary Therapies in Clinical Practice 39 (2020) 101166

Table 1 Table 2
Baseline characteristics for COVID-19 patients: Intervention versus Control Comparison of lung function, quality of life, and anxiety and depression between
group. the two groups before and after intervention (M � SD).
Characteristics Intervention group (n ¼ Control group (n ¼ P- Intervention group (n ¼ 36) Control group (n ¼ 36)
36) 36) values Measures
Pre Post 6 weeks After 6
Male, n, % 24 (66.7) 25 (69.4) 0.17 ago weeks
Age, years, (M�SD) 69.4 (8.0) 68.9 (7.6) 0.24
Pulmonary Function Test
BMI, kg/m2, 23.1 (3.5) 22.9 (3.9) 0.12
FEV1(L) 1.10 � 1.44 � 1.13 � 0.14 1.26 � 0.32
(M�SD)
0.08 0.25*#
CT features of lung lesions, n
FVC(L) 1.79 � 2.36 � 1.77 � 0.64 2.08 � 0.37
Multilobular lesion 25 (69.4) 23 (63.9) 0.33
0.53 0.49*#
Unilobar lesion 11 (30.6) 13 (36.1) 0.27
FEV1/FVC% 60.48 � 68.19 � 60.44 � 61.23 �
Pleural effusion 4 (11.1) 3 (8.3) 0.18
6.39 6.05*# 5.77 6.43
Comorbidity, n
TLCO % 60.3 � 78.1 � 60.7 � 12.0 63.0 � 13.4
Hypertension 10 (27.8) 8 (22.2) 0.56
11.3 12.3*#
T2DM 9 (25.0) 9 (25.0) 0.67
Exercise Capacity Test
Osteoporosis 8 (22.2) 6 (16.7) 0.41
6MWT, m 162.7 � 212.3 � 155.7 � 157.2 �
72.0 82.5*# 82.1 71.7
ADL
FIM 109.2 � 13 109.4 � 11.1 109.3 � 108.9 �
10.7 10.1
QoL (SF-36)
Physical health 52.4 � 6.2 71.6 � 7.6*# 53.2 � 7.7 54.1 � 7.5
Body role function 61.2 � 6.6 75.9 � 7.9*# 61.3 � 7.2 62.0 � 7.3
Physical pain 63.5 � 7.4 78.3 � 7.8*# 63.5 � 8.1 62.9 � 7.9
General health 61.8 � 7.7 74.2 � 7.9*# 61.8 � 8.4 61.4 � 6.9
Energy 60.6 � 6.9 75.6 � 7.1*# 60.5 � 7.1 61.2 � 6.3
Social function 59.4 � 7.2 69.8 � 6.4*# 59.5 � 7.0 58.9 � 6.6
Emotional role 61.4 � 6.9 75.7 � 7.0*# 61.4 � 7.3 60.8 � 7.3
function
Mental health 61.5 � 6.5 73.7 � 7.6*# 61.6 � 7.2 62.1 � 7.6
Anxiety and depression assessment
SAS score 56.3 � 8.1 47.4 � 6.3*# 55.8 � 7.4 54.9 � 7.3
SDS score 56.4 � 7.9 54.5 � 5.9 55.9 � 7.3 55.8 � 7.1

* Compared with the same group after intervention, P < 0.05.

Fig. 1. Changes in FEV1 and FVC over a 6 week time frame for the full cohort
of patients.
#
Compared with the control group after intervention, P < 0.05.
FVC: forced vital capacity; FEV1: forced expiratory volume at 1 s; DLCO:
diffusing lung capacity for carbon monoxide; 6MWT: 6-Minute Walk Test; FIM:
Functional Independence Measure.

Fig. 2. Changes in FEV1/FVC% and TLCO% over a 6 week time frame for the
full cohort of patients.
Fig. 3. Changes in 6 min walking distance over a 6 week time frame for the full
cohort of patients.
significant and also statistically significant compared with the control
group (Fig. 3, Table 2).
in patients aims at investigating the efficacy of this regimen and
ADL There was no significant improvement neither within the
revealing that 6-week respiratory rehabilitation significantly improves
intervention group nor compared with the control group (Table 2).
respiratory function, QoL, and anxiety and depression in elderly patients
QoL SF-36 scores in 8 dimensions, which were statistically signifi­
with COVID-19 and those without COPD.
cant within the intervention group and between the two groups, sug­
Under CT, patients with COVID-19 may have some residual fibrotic
gesting an improvement in QoL (Table 2).
lesions in the lungs following current treatment and discharge protocols
Anxiety and Depression Scores SAS and SDS scores decreased after
[7], which may affect the patient’s respiratory function. However, our
the intervention in the intervention group, but only anxiety was statis­
study found that pulmonary function was significantly improved after 6
tically significant within and between groups, and SDS scores were not
weeks of respiratory rehabilitation training. The reason may be that the
statistically significant within and between groups (Table 2).
rehabilitation training related to respiratory muscles in respiratory
rehabilitation training, and respiratory muscles include intercostal
4. Discussion
muscles, enthusiastic muscles, abdominal wall muscles, etc., which play
an important role in maintaining respiratory function. The decline of its
To our knowledge, this first randomized controlled trial of COVID-19

3
K. Liu et al.
function leads to dyspnea, abdominal breathing with labial constriction,
increases the expansion range of the breast muscle during breathing,
encourages patients to exercise the abdominal wall during breathing to
reduce chest wall movement, slows down the respiratory rate to reduce
power consumption, and increases pulmonary ventilation and blood
oxygen content [8].
Our exercise endurance measures assessed using the 6-min walk test
led to significant improvements in exercise capacity for the intervention
after a 6-week respiratory rehabilitation program. These results are
similar to those reported by Giansanti [9], who reported a significant
improvement in 6MWD after 6–9 weeks of respiratory rehabilitation,
suggesting an improvement in exercise capacity. However, exercise
training is the core of respiratory rehabilitation, its effect is affected by
the way, intensity, time and place of exercise training, and reasonable
exercise training has a positive impact on the physical and mental health
and QoL of COVID-19 patients [10]. Maki [11] et al. evaluated a study of
2504 patients with chronic obstructive non-disease who received exer­
cise intervention and found that the patients’ muscle strength increased
by 78%, muscle endurance increased by 92% and muscle mass increased
by 88%. The mechanism of action of exercise training on COPD reha­
bilitation is mostly related to the improvement of ventilation and gas
exchange function, cardiovascular function and limb muscle function in
patients [12]. Combined with our data, it is suggested that exercise
training has a significant improvement on exercise capacity in
COVID-19 patients.
In our study, living ability did not improve significantly after respi­
ratory rehabilitation, which may be due to the relatively short duration
of our respiratory rehabilitation. In addition, the independence of living
ability of our patients was weak, so the improvement of living ability
was not significant after short-term respiratory rehabilitation. In our
study, QoL was assessed using the SF-36, and there was an improvement
in QoL after 6 weeks of respiratory rehabilitation, which was statistically
significant with the control group. Studies have found that: respiratory
rehabilitation can improve the QoL of patients with COPD [6], asthma
[13], lung cancer after surgery [14]. Additionally, we found that 6
weeks of respiratory rehabilitation significantly improved anxiety in
elderly patients with COVID-19, which is consistent with the effect of
respiratory rehabilitation in COPD with Rebelo [15]. While in our pre­
vious study, it has been found that patients with COVID-19 experience
increased depression and anxiety after isolation treatment [16]. On the
other hand, positive changes in depression scores did not seem to be
influenced after the respiratory rehabilitation program. This is in line
with the findings of McNamara [17] et al. who reported that 6–9 weeks
of respiratory rehabilitation did not improve depression in elderly pa­
tients with COPD. The above results need to be further confirmed by
samples and longer respiratory rehabilitation studies.
Conclusions: Six-week respiratory rehabilitation can improve res­
piratory function, QoL and anxiety in elderly patients with COVID-19,
but it has no significant improvement in elderly depressive state and
activities of daily living.
4.1. Study limitations
This study has several limitations. Owing to the nature of the re­
covery and assessment environment, every effort has been made to blind
assessors and participants to group allocation, but this cannot be guar­
anteed. Therefore, we cannot rule out placebo effects, observer bias or
Complementary Therapies in Clinical Practice 39 (2020) 101166
experimenter bias in the current study. In addition, because at least 6
weeks of rehabilitation were required, we could only discharge patients
before February 6, which make our the sample size small; to address
these limitations, a further double-blind study with a large sample size at
multiple centers was required.
Contributors
WTZ, YDY, JPZ, Respiratory rehabilitation guidance and data
collection. KL and YC drafted the manuscript. YQL and KL revised the
final draft. YC. KL was the main supervisor and initiator of this study and
responsible for summarizing all data.
References
[1] Y.C. Wu, C.S. Chen, Y.J. Chan, The outbreak of COVID-19: an overview, J. Chin.
Med. Assoc. 83 (2020) 217–220, https://doi.org/10.1097/
JCMA.0000000000000270.
[2] M.A. Johansson, D. Saderi, Open peer-review platform for COVID-19 preprints,
Nature 579 (2020) 29, https://doi.org/10.1038/d41586-020-00613-4.
[3] A. Mikolajewska, M. Witzenrath, Community-acquired pneumonia in adults, Dtsch.
Med. Wochenschr. 145 (2020) 359–370, https://doi.org/10.1055/a-0993-0874.
[4] T. Jo, H. Yasunaga, N. Michihata, et al., Influence of Parkinsonism on outcomes of
elderly pneumonia patients, Park. Relat. Disord. 54 (2018) 25–29, https://doi.org/
10.1016/j.parkreldis.2018.03.028.
[5] N. Maki, H. Sakamoto, Y. Takata, et al., Effect of respiratory rehabilitation for frail
older patients with musculoskeletal disorders: a randomized controlled trial,
J. Rehabil. Med. 50 (2018) 908–913, https://doi.org/10.2340/16501977-2490.
[6] M.J. Prunera-Pardell, S. Padín-L� opez, A. Domenech-Del Rio, et al., Effectiveness of
a respiratory rehabilitation programme in patients with chronic obstructive
pulmonary disease, Enferm Clin. 28 (2018) 5–12, https://doi.org/10.1016/j.
enfcli.2017.11.001.
[7] A.J. Rodriguez-Morales, J.A. Cardona-Ospina, E. Guti� errez-Ocampo, et al., Clinical,
laboratory and imaging features of COVID-19: a systematic review and meta-
analysis, Travel Med. Infect. Dis. (2020) 101623, https://doi.org/10.1016/j.
tmaid.2020.101623.
[8] L. Cui, H. Liu, L. Sun, Multidisciplinary respiratory rehabilitation in combination
with non-invasive positive pressure ventilation in the treatment of elderly patients
with severe chronic obstructive pulmonary disease, Pak. J. Med. Sci. 35 (2019)
500–505, https://doi.org/10.12669/pjms.35.2.459.
[9] D. Giansanti, G. Maccioni, Toward the integration of devices for pulmonary
respiratory rehabilitation in telemedicine and e-health, Telemed. J. e Health 25 (3)
(2019) 257–259, https://doi.org/10.1089/tmj.2018.0057.
[10] Chinese Association of Rehabilitation Medicine, Recommendations for respiratory
rehabilitation of COVID-19 in adult, Zhonghua Jiehe He Huxi Zazhi 43 (2020)
E029, https://doi.org/10.3760/cma.j.cn112147-20200228-00206, 0.
[11] N. Maki, H. Sakamoto, Y. Takata, et al., Effect of respiratory rehabilitation for frail
older patients with musculoskeletal disorders: a randomized controlled trial,
J. Rehabil. Med. 50 (10) (2018) 908–913, https://doi.org/10.2340/16501977-
2490.
[12] J. Levy, H. Prigent, D. Bensmail, Respiratory rehabilitation in multiple sclerosis: a
narrative review of rehabilitation techniques, Ann. Phys. Rehabil. Med. 61 (1)
(2018 Jan) 38–45, https://doi.org/10.1016/j.rehab.2017.06.002.
[13] T. Schneeberger, I. Jarosch, J. Moll, et al., Ncreased asthma control after a 3-week
inpatient pulmonary rehabilitation program, Respir. Med. 165 (2020 Mar 8)
105930, https://doi.org/10.1016/j.rmed.2020.105930.
[14] K. Wytrychowski, A. Hans-Wytrychowska, P. Piesiak, et al., Pulmonary
rehabilitation in interstitial lung diseases: a review of the literature, Adv. Clin. Exp.
Med. 29 (2) (2020 Feb) 257–264, https://doi.org/10.17219/acem/115238.
[15] P. Rebelo, A. Oliveira, L. Andrade, et al., Minimal clinically important differences
for patient-reported outcome measures of fatigue in patients with COPD after
pulmonary rehabilitation, Chest (20) (2020 Mar 14) 30442–30446, https://doi.
org/10.1016/j.chest.2020.02.045, pii: S0012-3692.
[16] Kai Liu, Ying Chen, Duozhi Wu, et al., Effects of progressive muscle relaxation on
anxiety and sleep quality in patients with COVID-19, Compl. Ther. Clin. Pract. 39
(2020) 101132, https://doi.org/10.1016/j.ctcp.2020.101132.
[17] R.J. McNamara, M. Dale, Z.J. McKeough, Innovative strategies to improve the
reach and engagement in pulmonary rehabilitation, J. Thorac. Dis. 11 (Suppl 17)
(2019 Oct) S2192–S2199, https://doi.org/10.21037/jtd.2019.10.29.